Contribution of Intrinsic Alpha-Motoneuron Excitability to Disuse-Induced Muscle Weakness

内在α运动神经元兴奋性对废用性肌无力的影响

• 批准号: 10294948
• 负责人: Nathan Wages
• 金额: $ 7.05万
• 依托单位: OHIO UNIVERSITY ATHENS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10294948
• 关键词: Activities of Daily Living; Address; Anatomy; Animal Model; Area; Atrophic; Attenuated; Clinical; Computer Models; Computer Simulation; Data; Defect; Development; Educational workshop; Elbow; Elderly; Environment; Evoked Potentials; Fire - disasters; Flexor; Foundations; Frequencies; Goals; Grant; Human; Immobilization; Impairment; Individual; Intervention; Investigation; Knowledge; Link; Magnetism; Manuscripts; Measures; Mechanics; Mediating; Mentorship; Modality; Modeling; Motor; Motor Neurons; Muscle; Muscle Spindles; Muscle Weakness; Muscular Atrophy; Nature; Nerve Degeneration; Nervous system structure; Neurologic; Ohio; Output; Pharmaceutical Preparations; Pharmacology; Physiologic pulse; Physiology; Positioning Attribute; Production; Program Development; Property; Randomized; Reflex action; Research; Research Personnel; Resources; Role; Scientist; Spinal; Students; System; Techniques; Therapeutic Intervention; Training; Universities; Upper arm; Work; base; clinically significant; electric impedance; experimental study; faculty research; functional disability; functional restoration; improved; in vivo; indexing; muscle aging; muscle strength; muscular system; neuromechanism; physically handicapped; post intervention; recruit; sensory input; sex; symposium; technological innovation; tenure track; therapeutically effective; treatment strategy; vibration; young adult

PROJECT SUMMARY/ABSTRACT The work herein, will lay the foundation for a paradigm shift in treatment strategies, focusing on the nervous system, over the muscular system, when addressing physical impairments resulting from immobilization/disuse. The scientific focus on disuse-induced muscle weakness in recent decades has been primarily on muscle wasting (atrophy). Recent longitudinal investigations, and pharmacological drug trials, have clearly demonstrated muscle wasting to be moderately associated with weakness, suggesting a link with an impairment in the neurological system. Research has recently postulated a defect lies in mechanisms specific to the ɑ-motoneuron (MN), which encode repetitive firing. Historically, obtaining valid in vivo indices of human MN excitability has been difficult, but recent technological innovations have afforded scientists this capability. Notably, intrinsic MN excitability can be estimated via paired motor unit analysis (PMUA), and by applying cervicomedullary magnetic stimulation, to elicit a cervicomedullary evoked potential (CMEP). Attenuating muscle weakness, via effective therapeutic interventions, is a clinically significant issue necessitating an in-depth understanding of the spinal mechanism(s) mediating force production. Mechanical (muscle) vibration therapy is well-known to improve force output following prolonged periods of disuse, as vibration activates Ia afferents, which cause slow and fast MNs to increase their respective firing rates via a reflex arc. However, vibration during immobilization is drastically under-utilized as a modality to accelerate the restoration of functional capacity. The PI’s central hypothesis is intrinsic MN hypo-excitability is a key contributor to disuse-induced muscle weakness, while stimulation of Ia afferents is a key contributor to its impedance. In SA 1, the PI will determine if cast-immobilization (a model of disuse) decreases MN excitability. His hypothesis is immobilization will decrease ΔF and CMEP amplitude. In SA 2, the PI will determine if muscle vibration during immobilization restores MN excitability. His hypothesis is vibration will restore ΔF and CMEP amplitude. In SA 3, the PI will use data from SA 1 and 2 to determine how much of the change in force output after immobilization is due to changes in firing of slow vs. fast MNs via computer modeling. His hypotheses are: 1) fast MNs’ firing rate will decrease more significantly than that of slow MNs after immobilization, and 2) vibration will counteract intrinsic MN hypo-excitability by exciting slow and fast MNs to enhance their firing rates. The PI’s training plan will utilize “hands-on” computer simulation via animal models at Wright State University (WSU), significant computer modeling coursework at Ohio University (OU) and WSU, a Professional Development Program at Ohio State University, grantsmanship training/workshops, podium presentations at (inter)national conferences, manuscript compositions/submissions, grant/lab budgetary training, and student mentorship. The physical resources and the intellectual/institutional support available at WSU and OU, will not only provide an excellent environment for the PI to succeed in accomplishing the goals of this study, but will provide the PI with the initial steps in obtaining a tenure-track junior faculty research position.

项目摘要/摘要 这里的工作将为治疗策略的范式转移奠定基础，重点是紧张 当解决因固定/废弃而导致的身体障碍时，系统在肌肉系统上。 近几十年来，科学关注肌肉一直是肌肉的主要关注 浪费（萎缩）。最近的纵向研究和药物试验已清楚地证明 肌肉浪费与弱点相关，这表明与损害有联系 神经系统。研究最近发布了一个缺陷，这在于特定于motoneuron的机制 （MN），编码重复射击。从历史上看，获得人类MN兴奋性的有效体内指标具有 我们很困难，但是最近的技术创新为科学家提供了这种能力。值得注意的是，内在的Mn 可以通过配对运动单元分析（PMUA）和施加子宫内磁性估算兴奋性 刺激，引起子宫颈诱发的诱发电位（CMEP）。通过有效衰减肌肉无力 治疗干预措施是对脊柱的深入了解必要的临床意义问题 机制介导力产生。机械（肌肉）振动疗法众所周知以提高力 长时间停用时期的输出，因为振动激活了IA传入，这会导致缓慢而快速的MNS 通过反射弧提高其各自的射击率。但是，固定期间的振动急剧 用作未充分利用的方式来加速功能能力的恢复。 PI的中心假设是 固有的MN缺乏效果是导致肌肉无力的关键因素，同时刺激IA 传入是其阻抗的关键因素。在SA 1中，PI将确定铸造型铸造是否（模型 废弃）降低MN兴奋性。他的假设是固定化将减少ΔF和CMEP放大器。在 SA 2，PI将确定固定过程中的肌肉振动是否恢复MN的兴奋性。他的假设是 振动将恢复ΔF和CMEP放大器。在SA 3中，PI将使用SA 1和2的数据来确定如何 固定后力量输出的大部分变化是由于慢速发射与快速MN的变化所致 计算机建模。他的假设是：1）快速MN的发射速率将比缓慢降低。 固定后的MN和2）振动将通过令人兴奋的缓慢而快速抵消固有的MN缺陷性能 MNS以提高其发射率。 PI的培训计划将通过动物使用“动手”计算机模拟 赖特州立大学（WSU）的模型，俄亥俄州大学（OU）的重要计算机建模课程 以及WSU，俄亥俄州立大学的专业发展计划，授予技巧培训/讲习班， （国际）国家会议，手稿组成/提交，赠款/实验室预算的讲台演讲 培训和学生心态。物理资源和智力/机构支持 WSU和OU，不仅将为PI提供一个绝佳的环境，以成功完成目标 这项研究将为PI提供获得终身训练初级教师研究职位的初步步骤。